Volumetric Additive Manufacturing of SiOC by Xolography.

Additive manufacturing (AM) of ceramics has significantly contributed to advancements in ceramic fabrication, solving some of the difficulties of conventional ceramic processing and providing additional possibilities for the structure and function of components. However, defects induced by the layer-by-layer approach on which traditional AM techniques are based still constitute a challenge to address. This study presents the volumetric AM of a SiOC ceramic from a preceramic polymer using xolography, a linear volumetric AM process that allows to avoid the staircase effect typical of other vat photopolymerization techniques. Besides optimizing the trade-off between preceramic polymer content and transmittance, a pore generator is introduced to create transient channels for gas release before decomposition of the organic constituents and moieties, resulting in crack-free solid ceramic structures even at low ceramic yield. Formulation optimization alleviated sinking of printed parts during printing and prevented shape distortion. Complex solid and porous ceramic structures with a smooth surface and sharp features are fabricated under the optimized parameters. This work provides a new method for the AM of ceramics at µm/mm scale with high surface quality and large geometry variety in an efficient way, opening the possibility for applications in fields such as micromechanical systems and microelectronic components.

Contemporary Immunosuppression Management and 1-Year Outcomes in Dual Organ Heart Transplantation.

BACKGROUND: There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. METHODS: This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. RESULTS: A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. CONCLUSION: This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.

Cardio-Renal-Metabolic Outcomes Associated With the Use of GLP-1 Receptor Agonists After Heart Transplantation.

BACKGROUND: The use of glucagon-like-peptide 1 receptor agonists (GLP1-RA) has dramatically increased over the past 5 years for diabetes mellitus type 2 (T2DM) and obesity. These comorbidities are prevalent in adult heart transplant (HT) recipients. However, there are limited data evaluating the efficacy of this drug class in this population. The aim of the current study was to describe cardiometabolic changes in HT recipients prescribed GLP1-RA at a large-volume transplant center. METHODS: We retrospectively reviewed all adult HT recipients who received GLP1-RA after HT for a minimum of 1-month. Cardiometabolic parameters including body mass index (BMI), lipid panel, hemoglobin A1C, estimated glomerular filtration rate (eGFR), and NT-proBNP were compared prior to initiation of the drug and at most recent follow-up. We also evaluated for significant dose adjustments to immunosuppression after drug initiation and adverse effects leading to drug discontinuation. RESULTS: Seventy-four patients were included (28% female, 53% White, 20% Hispanic) and followed for a median of 383 days [IQR 209, 613] on a GLP1-RA. The majority of patients (n = 56, 76%) were prescribed semaglutide. The most common indication for prescription was T2DM alone (n = 33, 45%), followed by combined T2DM and obesity (n = 26, 35%). At most recent follow-up, mean BMI decreased from 33.3 to 31.5 kg/m2 (p < 0.0001), HbA1C from 7.3% to 6.7% (p = 0.005), LDL from 78.6 to 70.3 mg/dL (p = 0.018) and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002). CONCLUSION: HT recipients prescribed GLP1-RA therapy showed improved glycemic control, weight loss, and cholesterol levels during the study follow-up period. GLP1-RA were well tolerated and were rarely associated with changes in immunosuppression dosing.

Comparative Analysis of Ischemia-Reperfusion Injury in Heart Transplantation: A Single-Center Study Evaluating Conventional Ice-Cold Storage versus the Paragonix SherpaPak Cardiac Transport System.

BACKGROUND: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). METHODS: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. RESULTS: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups. CONCLUSION: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Clinical attachment loss is cross-sectionally associated with elevated glucose among adults without diabetes.

AIM: We investigated whether periodontal measures are cross-sectionally associated with prediabetes and cardiometabolic biomarkers among non-diabetic younger adults. MATERIALS AND METHODS: One thousand seventy-one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full-mouth clinical attachment loss (fm-CAL), probing depth (fm-PD) and bleeding on probing were ascertained. Interproximal CAL (i-CAL) and probing depths (i-PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA-IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. RESULTS: Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i-CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i-CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i-PD ≥3 mm showed elevated natural-log-HOMA-IR after adjustment (0%-12% of sites = 0.33 [0.03], 13%-26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04). CONCLUSIONS: i-CAL (vs. fm-CAL) was associated with elevated fasting glucose and prediabetes, whereas i-PD (vs. fm-PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

Pre-operative pectoralis muscle area index is associated with biomarkers of inflammation and endotoxemia and predicts clinical outcomes after left ventricular assist device implantation: A cohort study.

BACKGROUND: Pre-left ventricular assist device (LVAD) pectoralis muscle assessment, an estimate of sarcopenia, has been associated with postoperative mortality and gastrointestinal bleeding, though its association with inflammation, endotoxemia, length-of-stay (LOS), and readmissions remains underexplored. METHODS: This was a single-center cohort study of LVAD patients implanted 1/2015-10/2018. Preoperative pectoralis muscle area was measured on chest computed tomography (CT), adjusted for height squared to derive pectoralis muscle area index (PMI). Those with PMI in the lowest quintile were defined as low-PMI cohort; all others constituted the reference cohort. Biomarkers of inflammation (interleukin-6, adiponectin, tumor necrosis factor-α [TNFα]) and endotoxemia (soluble (s)CD14) were measured in a subset of patients. RESULTS: Of the 254 LVAD patients, 95 had a preoperative chest CT (median days pre-LVAD: 7 [IQR 3-13]), of whom 19 (20.0%) were in the low-PMI cohort and the remainder were in the reference cohort. Compared with the reference cohort, the low-PMI cohort had higher levels of sCD14 (2594 vs. 1850 ng/mL; p = 0.04) and TNFα (2.9 vs. 1.9 pg/mL; p = 0.03). In adjusted analyses, the low-PMI cohort had longer LOS (incidence rate ratio 1.56 [95% confidence interval 1.16-2.10], p = 0.004) and higher risk of 90-day and 1-year readmissions (subhazard ratio 5.48 [1.88-16.0], p = 0.002; hazard ratio 1.73 [1.02-2.94]; p = 0.04, respectively). CONCLUSIONS: Pre-LVAD PMI is associated with inflammation, endotoxemia, and increased LOS and readmissions.

Unplanned hospital readmissions following HeartMate 3 implantation: Readmission rates, causes, and impact on survival.

BACKGROUND: Hospital readmissions following left ventricular assist device (LVAD) remain a frequent comorbidity, associated with decreased quality of life and increased resources utilization. This study sought to determine causes, predictors, and impact on survival of hospitalizations during HeartMate 3 (HM3) support. METHODS: All patients implanted with HM3 between November 2014 to December 2019 at Columbia University Irving Medical Center were consecutively enrolled in the study. Demographics and clinical characteristics from the index admission and the first outpatient visit were collected and used to estimate 1-year and 900-day readmission-free survival and overall survival. Multivariable analysis was performed for subsequent readmissions. RESULTS: Of 182 patients who received a HM3 LVAD, 167 (92%) were discharged after index admission and experienced 407 unplanned readmissions over the median follow up of 727 (interquartile range (IQR): 410.5, 1124.5) days. One-year and 900-day mean cumulative number of all-cause unplanned readmissions was 0.43 (95%CI, 0.36, 0.51) and 1.13 (95%CI, 0.99, 1.29). The most frequent causes of rehospitalizations included major infections (29.3%), bleeding (13.2%), device-related (12.5%), volume overload (7.1%), and other (28%). One-year and 900-day survival free from all-cause readmission was 38% (95%CI, 31-46%) and 16.6% (95%CI, 10.3-24.4%). One-year and 900-day freedom from 2, 3, and ≥4 readmissions were 60.7%, 74%, 74.5% and 26.2%, 33.3%, 41.3%. One-year and 900-day survival were unaffected by the number of readmissions and remained >90%. Male sex, ischemic etiology, diabetes, lower serum creatinine, longer duration of index hospitalization, and a history of readmission between discharge and the first outpatient visit were associated with subsequent readmissions. CONCLUSIONS: Unplanned hospital readmissions after HM3 are common, with infections and bleeding accounting for the majority of readmissions. Irrespective of the number of readmissions, one-year survival remained unaffected.

Extracellular Vesicles and Immunity: At the Crossroads of Cell Communication.

Extracellular vesicles (EVs), comprising exosomes and microvesicles, are small membranous structures secreted by nearly all cell types. They have emerged as crucial mediators in intercellular communication, playing pivotal roles in diverse physiological and pathological processes, notably within the realm of immunity. These roles go beyond mere cellular interactions, as extracellular vesicles stand as versatile and dynamic components of immune regulation, impacting both innate and adaptive immunity. Their multifaceted involvement includes immune cell activation, antigen presentation, and immunomodulation, emphasising their significance in maintaining immune homeostasis and contributing to the pathogenesis of immune-related disorders. Extracellular vesicles participate in immunomodulation by delivering a wide array of bioactive molecules, including proteins, lipids, and nucleic acids, thereby influencing gene expression in target cells. This manuscript presents a comprehensive review that encompasses in vitro and in vivo studies aimed at elucidating the mechanisms through which EVs modulate human immunity. Understanding the intricate interplay between extracellular vesicles and immunity is imperative for unveiling novel therapeutic targets and diagnostic tools applicable to various immunological disorders, including autoimmune diseases, infectious diseases, and cancer. Furthermore, recognising the potential of EVs as versatile drug delivery vehicles holds significant promise for the future of immunotherapies.

Guardians under Siege: Exploring Pollution's Effects on Human Immunity.

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body's defense systems going beyond the well-established associations with defense systems and delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health.

Effect of PFDS on the immobilization of Cs+ by metakaolin-based geopolymers in complex environments.

Metakaolin-based geopolymers are very promising materials for improving the safety of low and intermediate level radioactive waste disposal, with respect to ordinary Portland cement, due to their excellent immobilization performance for Cs+ and superior chemical stability. However, their application is limited by the fact that the leaching behavior of Cs+ is susceptible to the presence of other ions in the environment. Here, we propose a way to modify a geopolymer using perfluorodecyltriethoxysilane (PDFS), successfully reducing the leaching rate of Cs+ in the presence of multiple competitive cations due to blocking the diffusion of water. The leachability index of the modified samples in deionized water and highly concentrated saline water reached 11.0 and 8.0, respectively. The reaction mechanism between PDFS and geopolymers was systematically investigated by characterizing the microstructure and chemical bonding of the material. This work provides a facile and successful approach to improve the immobilization of Cs ions by geopolymers in real complex environments, and it could be extended to further improve the reliability of geopolymers used in a range of applications.

Dietary nitrate intake and net nitrite-generating capacity of the oral microbiome interact to enhance cardiometabolic health: Results from the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Background: We investigated the association between dietary nitrate intake and early clinical cardiometabolic risk biomarkers, and explored whether the oral microbiome modifies the association between dietary nitrate intake and cardiometabolic biomarkers. Methods: Cross-sectional data from 668 (mean [SD] age 31 [9] years, 73% women) participants was analyzed. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a validated US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic risk biomarkers included systolic and diastolic blood pressure, HbA1c, glucose, insulin, and insulin resistance (HOMA-IR), and were regressed on nitrate intake tertiles in adjusted multivariable linear models. Results: Mean nitrate intake was 190[171] mg/day. Higher nitrate intake was associated with lower insulin, and HOMA-IR but particularly among participants with low abundance of oral nitrite enriching bacteria. For example, among participants with a low MINES, mean insulin[95%CI] levels in high vs. low dietary nitrate consumers were 5.8[5.3,6.5] vs. 6.8[6.2,7.5] (p=0.004) while respective insulin levels were 6.0[5.4,6.6] vs. 5.9[5.3,6.5] (p=0.76) among partcipants with high MINES (interaction p=0.02). Conclusion: Higher dietary nitrate intake was only associated with lower insulin and insulin resistance among individuals with reduced capacity for oral microbe-induced nitrite enrichment. These findings have implications for future precision medicine-oriented approaches that might consider assessing the oral microbiome prior to enrollment into dietary interventions or making dietary recommendations.

Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant Properties of the Egadi Island Endemic Brassica macrocarpa Guss Leaf Extract.

The genus Brassica is an important source of food in the Mediterranean diet with documented nutritional and medicinal properties. However, few studies have investigated the phytochemical composition and the biological activity of wild Sicilian taxa. Thus, we aimed to study the chemical profile and the antioxidant potential, in vitro and in LPS-stimulated RAW 264.7 cells, of a methanolic extract of leaves of wild Brassica macrocarpa Guss (B. macrocarpa) (Egadi Islands; Sicily-Italy). B. macrocarpa methanolic extract showed a large amount of glucosinolates and different phenolic compounds. It exhibited antioxidant activity in the DPPH assay and in LPS-stimulated RAW 264.7 cells, being able to reduce NO and ROS levels and NOS2 mRNA expression. Our study demonstrated that Sicilian B. macrocarpa methanolic extract, in LPS-stimulated macrophages, efficiently counteracts oxidative stress and displays radical scavenging activity. Future studies are required to identify the contribution of the single phytocomponents, to characterize the action mechanism, and to reveal possible applications in human health.

Alterations in the sarcopenia index are associated with inflammation, gut, and oral microbiota among heart failure, left ventricular assist device, and heart transplant patients.

BACKGROUND: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD), and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. METHODS: We enrolled 460 HF, LVAD, and HT patients. Repeated measures pre/post-procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum creatinine/cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S ribosomal ribonucleic acid sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and (1) New York Heart Association class; (2) pre- versus post-LVAD or HT; and (3) biomarkers of inflammation and microbial diversity. RESULTS: Median (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32, 0.05). Ln-SI decreased across worsening HF class, further declined at 1 month after LVAD and HT, and rebounded over time. Ln-SI was correlated with inflammation (r = -0.28, p < 0.01), gut (r = 0.28, p < 0.01), and oral microbial diversity (r = 0.24, p < 0.01). These associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. The presence of the gut taxa Roseburia inulinivorans was associated with increased SI. CONCLUSIONS: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and were significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes.

Medium-Term Outcomes of Concomitant Aortic Valve Repair in Patients with Continuous-Flow Left Ventricular Assist Device.

OBJECTIVE: Our objective was to analyze the development of aortic insufficiency in patients who received central aortic valve repair when undergoing continuous-flow left ventricular assist device implantation. METHODS: We conducted a retrospective review of patients who underwent HeartMate II or 3 (Abbott Lab) implantation between 2004 and 2022. Ninety-four patients were excluded from analysis for history of aortic valve procedures, a bicuspid aortic valve, baseline trace aortic insufficiency, or other concomitant aortic valve procedure. Patients who had ≥ mild aortic insufficiency had concomitant aortic valve repair. Clinical characteristics, serial echocardiograms, and outcomes were determined. RESULTS: Of the 656 patients who underwent HeartMate II or 3 implantation, 105 patients (59 HeartMate II and 46 HeartMate 3) met study criteria. Median age was 68 years [60-74 years], 91.4% [n=96] were male, 54.4% [n=56] were white, and 68.6% [n=72] received support as destination therapy. Preoperative aortic insufficiency degree was 54.3% (n=57) mild, 23.8% (n=25) mild-to-moderate, 20.0% (n=21) moderate, 1.0% (n=1) moderate-to-severe, 1.0% (n=1) severe. In hospital mortality was 5.7% [n=6]. Freedom from ≥ moderate aortic insufficiency was 96.4% (95%CI: 92.5%-100%), 93.3% (95%CI: 87.6%-99.2%), and 91.0% (95%CI: 84.1%-98.5%) at 1-year, 2-year, and 3-year post-implantation, respectively. One HeartMate II patient experienced severe aortic insufficiency and was treated with a heart transplant. Three-year survival was 63.4% [95%CI: 52.9%-75.9%]. CONCLUSIONS: Central aortic valve repair may be an effective technique to mitigate aortic insufficiency in HeartMate II and 3. A larger cohort study with longer duration of follow up is warranted to further investigate the clinical impact.

Kidney Function Assessment Using Cystatin C and Serum Creatinine in Heart Transplantation Recipients: Implications for Valganciclovir Dosing.

BACKGROUND: Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in extrarenal variables (e.g., muscle mass). Cystatin C (cysC) is less influenced by muscle mass; however, obesity and steroid use may increase cysC levels. Herein, we: i) longitudinally compared changes in eGFRcysC and eGFRsCr among HT recipients; ii) investigated the association of body mass index (BMI), steroid use and muscle mass with discrepancies between eGFRs; and iii) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing. METHODS: cysC and sCr were measured in 294 blood samples obtained from 80 HT recipients. Intra-individual differences between eGFRs (eGFRdiffcysC-sCr) were calculated. Negative eGFRdiffcysC-sCr values correspond to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n=21), pectoralis muscle measures were derived from computed tomography scans. RESULTS: Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr -28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient post-operative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Conversely, pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction. CONCLUSIONS: Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.

Validation of the HeartMate 3 survival risk score in a large left ventricular assist device center.

OBJECTIVE: The HeartMate 3 survival risk score was recently validated in the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 to predict patient-specific survival in HeartMate 3 left ventricular assist device candidates. The HeartMate 3 survival risk score stratifies individuals into tertiles according to survival probability. METHODS: We performed a single-center retrospective review of all HeartMate 3 left ventricular assist device recipients between September 2017 and August 2022. Baseline characteristics were collected from the electronic medical records. HeartMate 3 survival risk scores were calculated for all eligible patients. One- and 2-year Kaplan-Meier survival analyses were conducted. A univariate and multivariable Cox regression model was used to identify predictors. RESULTS: A total of 181 patients were included in this final analysis. The median age was 62 years, 83% were male, and 26% were Interagency Registry for Mechanically Assisted Circulatory Support Profile 1. The mean HeartMate 3 survival risk score for the entire cohort was 2.66 ± 0.66. Two-year survivals in the high, average, and low survival groups were 93.5% ± 3.2%, 81.6% ± 7.4%, and 82.0% ± 6.6%, respectively. As a continuous variable, the unadjusted HeartMate 3 survival risk score was a significant predictor of mortality (hazard ratio, 2.20; 95% CI, 1.08-4.45; P = .029). The areas under the curve were 0.70 and 0.66 at 1 and 2 years, respectively. We were unable to demonstrate the discriminatory ability of the HeartMate 3 survival risk score using the original stratification, but we found significantly increased survival in the high survival group using a binary cutoff (hazard ratio, 4.8; 95% CI, 1.01-20.9; P = .038). CONCLUSIONS: The unadjusted HeartMate 3 survival risk score was associated with postimplant survival in patients outside of the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 but did not remain an independent predictor after adjusting for ischemic etiology and severe diabetes. The HeartMate 3 survival risk score was able to identify patients at high survival using a binary cutoff, but we were unable to demonstrate its discriminatory ability among the previously published risk tertiles.

Added prognostic value of visually estimated coronary artery calcium among heart transplant recipients.

BACKGROUND: Cardiac hybrid positron emission tomography/computed tomography (PET/CT) has become a valid screening modality for cardiac allograft vasculopathy (CAV) following heart transplantation (HT). Visually estimated coronary artery calcium (VECAC) can be quantified from CT images obtained as part of PET/CT and has been shown to be associated with adverse cardiovascular outcomes in coronary artery disease. We investigated the prognostic value of VECAC following HT. METHODS: A retrospective analysis of 430 consecutive adult HT patients who underwent 13N-ammonia cardiac PET/CT from 2016 to 2019 with follow-up through October 15, 2022, was performed. VECAC categories included: VECAC 0, VECAC 1-9, VECAC 10-99, and VECAC 100+. The association between VECAC categories and outcomes was assessed using univariable and multivariable proportional hazards regression. The primary outcome was death/retransplantation. RESULTS: The cohort was 73% male, 33% had diabetes, 67% had estimated glomerular filtration rate <60 ml/min, median age was 61 years, and median time since HT was 7.5 years. VECAC alone was insufficiently sensitive to screen for CAV. During a median follow-up of 4.2 years ninety patients experienced death or retransplantation. Compared with those with VECAC 0, patients VECAC 10-99 (HR 2.25, 95% CI 1.23-4.14, p = 0.009) and VECAC 100+ (HR 3.42, 95% CI 1.96-5.99, p < 0.001) experienced an increased risk of death/retransplantation. The association was similar for cardiovascular death and cardiovascular hospitalization. After adjusting for other predictors of death/retransplantation, VECAC 10-99 (VECAC 10-99: aHR 1.95, 95% CI 1.03-3.71 p = 0.04) and VECAC 100+ (VECAC 100+: aHR 2.33, 95% CI 1.17-4.63, p = 0.02) remained independently associated with death/retransplantation. CONCLUSIONS: VECAC is an independent prognostic marker of death/retransplantation following HT and merits inclusion as a part of post-HT surveillance PET/CT.